Hyaluronic acid and epidermal growth factor improved the bovine embryo quality by regulating the DNA methylation and expression patterns of the focal adhesion pathway
Autoři:
Mohammed Saeed-Zidane aff001; Dawit Tesfaye aff001; Yousri Mohammed Shaker aff002; Ernst Tholen aff001; Christiane Neuhoff aff001; Franca Rings aff003; Eva Held aff001; Michael Hoelker aff001; Karl Schellander aff001; Dessie Salilew-Wondim aff001
Působiště autorů:
Institute of Animal Science, Department of Animal Breeding and Husbandry, University of Bonn, Bonn, Germany
aff001; Animal and Poultry Physiology Department, Animal and Poultry Production Division, Desert Research Center, Mataria, Cairo, Egypt
aff002; Teaching and Research Station Frankenforst, Faculty of Agriculture, University of Bonn, Königswinter, Germany
aff003; Center of Integrated Dairy Research, University of Bonn, Bonn, Germany
aff004
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0223753
Souhrn
Focal adhesion pathway is one of the key molecular pathways affected by suboptimal culture conditions during embryonic development. The epidermal growth factor (EGF) and hyaluronic acid (HA) are believed to be involved in the focal adhesion pathway function by regulating the adherence of the molecules to the extracellular matrix. However, regulatory and molecular mechanisms through which the EGF and HA could influence the embryo development is not clear. Therefore, this study aimed to investigate the effect of continued or stage specific supplementation of EGF and/or HA on the developmental competence and quality of bovine preimplantation embryos and the subsequent consequences on the expression and DNA methylation patterns of genes involved in the focal adhesion pathway. The results revealed that, the supplementation of EGF or HA from zygote to the blastocysts stage reduced the level of reactive oxygen species and increased hatching rate after thawing. On the other hand, HA decreased the apoptotic nuclei and increased blastocyst compared to EGF supplemented group. Gene expression and DNA methylation analysis in the resulting blastocysts indicated that, combined supplementation of EGF and HA increased the expression of genes involved in focal adhesion pathway while supplementation of EGF, HA or a combination of EGF and HA during the entire preimplantation period changed the DNA methylation patterns of genes involved in focal adhesion pathway. On the other hand, blastocysts developed in culture media supplemented with EGF + HA until the 16-cell stage exhibited higher expression level of genes involved in focal adhesion pathway compared to those supplemented after the 16-cell stage. Conversely, the DNA methylation level of candidate genes was increased in the blastocysts obtained from embryos cultured in media supplemented with EGF + HA after 16-cell stage. In conclusion, supplementation of bovine embryos with EGF and/or HA during the entire preimplantation period or in a stage specific manner altered the DNA methylation and expression patterns of candidate genes involved in the focal adhesion pathway which was in turn associated with the observed embryonic developmental competence and quality.
Klíčová slova:
DNA methylation – Gene expression – Embryos – Culture media – Promoter regions – Blastocysts – Focal adhesions – Zygotes
Zdroje
1. Lonergan P, Rizos D, Gutiérrez-Adán A, Fair T, Boland MP. Effect of culture environment on embryo quality and gene expression—experience from animal studies. Reprod Biomed Online. 2003;7(6):657–63. doi: 10.1016/s1472-6483(10)62088-3 14748964
2. Gad A, Hoelker M, Besenfelder U, Havlicek V, Cinar U, Rings F, et al. Molecular mechanisms and pathways involved in bovine embryonic genome activation and their regulation by alternative in vivo and in vitro culture conditions. Biol Reprod. 2012;87(4):100. doi: 10.1095/biolreprod.112.099697 22811576
3. Salilew-Wondim D, Fournier E, Hoelker M, Saeed-Zidane M, Tholen E, Looft C, et al. Genome-Wide DNA Methylation Patterns of Bovine Blastocysts Developed In Vivo from Embryos Completed Different Stages of Development In Vitro. PLoS One. 2015;10(11):e0140467. doi: 10.1371/journal.pone.0140467 26536655
4. Salilew-Wondim D, Saeed-Zidane M, Hoelker M, Gebremedhn S, Poirier M, Om Pandey H, et al. Genome-wide DNA methylation patterns of bovine blastocysts derived from in vivo embryos subjected to in vitro culture before, during or after embryonic genome activation. BMC Genomics. 2018;19:424. doi: 10.1186/s12864-018-4826-3 29859035
5. Wrighton KH. Cell adhesion: the 'ins' and 'outs' of integrin signalling. Nat Rev Mol Cell Biol. 2013;14(12):752.
6. Kaneko Y, Lecce L, Day ML, Murphy CR. Focal adhesion kinase localizes to sites of cell-to-cell contact in vivo and increases apically in rat uterine luminal epithelium and the blastocyst at the time of implantation. J Morphol. 2012;273(6):639–50. doi: 10.1002/jmor.20010 22322452
7. Bladt F, Aippersbach E, Gelkop S, Strasser GA, Nash P, Tafuri A, et al. The murine Nck SH2/SH3 adaptors are important for the development of mesoderm-derived embryonic structures and for regulating the cellular actin network. Mol Cell Biol. 2003;23(13):4586–97. doi: 10.1128/MCB.23.13.4586-4597.2003 12808099
8. Renshaw MW, Price LS, Schwartz MA. Focal adhesion kinase mediates the integrin signaling requirement for growth factor activation of MAP kinase. J Cell Biol. 1999;147(3):611–8. doi: 10.1083/jcb.147.3.611 10545504
9. Sinclair KD, Rooke JA, McEvoy TG. Regulation of nutrient uptake and metabolism in pre-elongation ruminant embryos. Reprod Suppl. 2003;61):371–85.
10. Adamson ED. Activities of growth factors in preimplantation embryos. J Cell Biochem. 1993;53(4):280–7. doi: 10.1002/jcb.240530403 8300744
11. Wei Z, Park KW, Day BN, Prather RS. Effect of epidermal growth factor on preimplantation development and its receptor expression in porcine embryos. Mol Reprod Dev. 2001;60(4):457–62. doi: 10.1002/mrd.1110 11746956
12. Cebrian-Serrano A, Salvador I, Silvestre MA. Beneficial effect of two culture systems with small groups of embryos on the development and quality of in vitro-produced bovine embryos. Anat Histol Embryol. 2014;43(1):22–30. doi: 10.1111/ahe.12043 23488942
13. Block J, Bonilla L, Hansen PJ. Effect of addition of hyaluronan to embryo culture medium on survival of bovine embryos in vitro following vitrification and establishment of pregnancy after transfer to recipients. Theriogenology. 2009;71(7):1063–71. doi: 10.1016/j.theriogenology.2008.11.007 19157530
14. Reis e Silva AR, Bruno C, Fleurot R, Daniel N, Archilla C, Peynot N, et al. Alteration of DNA demethylation dynamics by in vitro culture conditions in rabbit pre-implantation embryos. Epigenetics. 2012;7(5):440–6. doi: 10.4161/epi.19563 22419129
15. Katari S, Turan N, Bibikova M, Erinle O, Chalian R, Foster M, et al. DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet. 2009;18(20):3769–78. doi: 10.1093/hmg/ddp319 19605411
16. Park YS, Lin YC. Effect of epidermal growth factor (EGF) and defined simple media on in vitro bovine oocyte maturation and early embryonic development. Theriogenology. 1993;39(2):475–84. doi: 10.1016/0093-691x(93)90390-q 16727227
17. Mtango NR, Varisanga MD, Dong YJ, Rajamahendran R, Suzuki T. Growth factors and growth hormone enhance in vitro embryo production and post-thaw survival of vitrified bovine blastocysts. Theriogenology. 2003;59(5–6):1393–402. doi: 10.1016/s0093-691x(02)01163-9 12527085
18. Oyamada T, Iwayama H, Fukui Y. Additional effect of epidermal growth factor during in vitro maturation for individual bovine oocytes using a chemically defined medium. Zygote. 2004;12(2):143–50. 15460109
19. Ahumada CJ, Salvador I, Cebrian-Serrano A, Lopera R, Silvestre MA. Effect of supplementation of different growth factors in embryo culture medium with a small number of bovine embryos on in vitro embryo development and quality. Animal. 2013;7(3):455–62. doi: 10.1017/S1751731112001991 23121725
20. Furnus CC, Matos DG de, Martinez AG. Effect of hyaluronic acid on development of in vitro produced bovine embryos. Theriogenology. 1998;49(8):1489–99. doi: 10.1016/s0093-691x(98)00095-8 10732013
21. Palasz AT, Rodriguez-Martinez H, Beltran-Brena P, Perez-Garnelo S, Martinez MF, Gutierrez-Adan A, La Fuente J de. Effects of hyaluronan, BSA, and serum on bovine embryo in vitro development, ultrastructure, and gene expression patterns. Mol Reprod Dev. 2006;73(12):1503–11. doi: 10.1002/mrd.20516 16902955
22. Palasz AT, Brena PB, Martinez MF, Perez-Garnelo SS, Ramirez MA, Gutierrez-Adan A, La Fuente J de. Development, molecular composition and freeze tolerance of bovine embryos cultured in TCM-199 supplemented with hyaluronan. Zygote. 2008;16(1):39–47. doi: 10.1017/S0967199407004467 18221580
23. Handyside AH, Hunter S. A rapid procedure for visualising the inner cell mass and trophectoderm nuclei of mouse blastocysts in situ using polynucleotide-specific fluorochromes. J Exp Zool. 1984;231(3):429–34. doi: 10.1002/jez.1402310317 6209359
24. Wolf E, Arnold GJ, Bauersachs S, Beier HM, Blum H, Einspanier R, et al. Embryo-maternal communication in bovine—strategies for deciphering a complex cross-talk. Reprod Domest Anim. 2003;38(4):276–89. 12887567
25. Wu C. Focal adhesion: a focal point in current cell biology and molecular medicine. Cell Adh Migr. 2007;1(1):13–8. doi: 10.4161/cam.1.1.4081 19262093
26. Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: normal and abnormal functions. Endocrinology. 2004;145(12):5439–47. doi: 10.1210/en.2004-0959 15331580
27. Goodsell DS. The molecular perspective: epidermal growth factor. Stem Cells. 2003;21(6):702–3. doi: 10.1634/stemcells.21-6-702 14595130
28. Fujihara M, Comizzoli P, Keefer CL, Wildt DE, Songsasen N. Epidermal growth factor (EGF) sustains in vitro primordial follicle viability by enhancing stromal cell proliferation via MAPK and PI3K pathways in the prepubertal, but not adult, cat ovary. Biol Reprod. 2014;90(4):86. doi: 10.1095/biolreprod.113.115089 24554736
29. Prochazka R, Petlach M, Nagyova E, Nemcova L. Effect of epidermal growth factor-like peptides on pig cumulus cell expansion, oocyte maturation, and acquisition of developmental competence in vitro: comparison with gonadotropins. Reproduction. 2011;141(4):425–35. doi: 10.1530/REP-10-0418 21239527
30. Lorenzo PL, Illera MJ, Illera JC, Illera M. Enhancement of cumulus expansion and nuclear maturation during bovine oocyte maturation in vitro by the addition of epidermal growth factor and insulin-like growth factor I. J Reprod Fertil. 1994;101(3):697–701. doi: 10.1530/jrf.0.1010697 7966028
31. Shabankareh HK, Zandi M. Developmental potential of sheep oocytes cultured in different maturation media: effects of epidermal growth factor, insulin-like growth factor I, and cysteamine. Fertil Steril. 2010;94(1):335–40. doi: 10.1016/j.fertnstert.2009.01.160 19324348
32. Sirisathien S, Hernandez-Fonseca HJ, Brackett BG. Influences of epidermal growth factor and insulin-like growth factor-I on bovine blastocyst development in vitro. Anim Reprod Sci. 2003;77(1–2):21–32. 12654525
33. Song HJ, Kang EJ, Maeng GH, Ock SA, Lee SL, Yoo JG, et al. Influence of epidermal growth factor supplementation during in vitro maturation on nuclear status and gene expression of canine oocytes. Res Vet Sci. 2011;91(3):439–45. doi: 10.1016/j.rvsc.2010.09.003 20888022
34. Neira JA, Tainturier D, Pena MA, Martal J. Effect of the association of IGF-I, IGF-II, bFGF, TGF-beta1, GM-CSF, and LIF on the development of bovine embryos produced in vitro. Theriogenology. 2010;73(5):595–604. doi: 10.1016/j.theriogenology.2009.10.015 20035987
35. Eberwein P, Laird D, Schulz S, Reinhard T, Steinberg T, Tomakidi P. Modulation of focal adhesion constituents and their down-stream events by EGF: On the cross-talk of integrins and growth factor receptors. Biochim Biophys Acta. 2015;1853(10 Pt A):2183–98.
36. Lee CN, Ax RL. Concentrations and composition of glycosaminoglycans in the female bovine reproductive tract. J Dairy Sci. 1984;67(9):2006–9. doi: 10.3168/jds.S0022-0302(84)81536-2 6436345
37. Suchanek E, Simunic V, Juretic D, Grizelj V. Follicular fluid contents of hyaluronic acid, follicle-stimulating hormone and steroids relative to the success of in vitro fertilization of human oocytes. Fertil Steril. 1994;62(2):347–52. doi: 10.1016/s0015-0282(16)56890-3 8034084
38. Ohta N, Saito H, Kaneko T, Yoshida M, Takahashi T, Saito T, et al. Soluble CD44 in human ovarian follicular fluid. J Assist Reprod Genet. 2001;18(1):21–5. doi: 10.1023/A:1026494528415 11292991
39. Archibong AE, Petters RM, Johnson BH. Development of porcine embryos from one- and two-cell stages to blastocysts in culture medium supplemented with porcine oviductal fluid. Biol Reprod. 1989;41(6):1076–83. doi: 10.1095/biolreprod41.6.1076 2624868
40. Laurent TC, Fraser JR. Hyaluronan. FASEB J. 1992;6(7):2397–404. 1563592
41. Qhattal HSS, Hye T, Alali A, Liu X. Hyaluronan polymer length, grafting density, and surface poly(ethylene glycol) coating influence in vivo circulation and tumor targeting of hyaluronan-grafted liposomes. ACS Nano. 2014;8(6):5423–40. doi: 10.1021/nn405839n 24806526
42. Oommen OP, Duehrkop C, Nilsson B, Hilborn J, Varghese OP. Multifunctional Hyaluronic Acid and Chondroitin Sulfate Nanoparticles: Impact of Glycosaminoglycan Presentation on Receptor Mediated Cellular Uptake and Immune Activation. ACS Appl Mater Interfaces. 2016;8(32):20614–24. doi: 10.1021/acsami.6b06823 27468113
43. Donejko M, Rysiak E, Galicka E, Terlikowski R, Glazewska EK, Przylipiak A. Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol. Drug Des Devel Ther. 2017;11):669–76. doi: 10.2147/DDDT.S125843 28293103
44. Kaneko T, Saito H, Toya M, Satio T, Nakahara K, Hiroi M. Hyaluronic acid inhibits apoptosis in granulosa cells via CD44. J Assist Reprod Genet. 2000;17(3):162–7. doi: 10.1023/A:1009470206468 10911577
45. Turley E, Moore D. Hyaluronate binding proteins also bind to fibronectin, laminin and collagen. Biochem Biophys Res Commun. 1984;121(3):808–14. doi: 10.1016/0006-291x(84)90750-2 6204647
46. Marei WF, Ghafari F, Fouladi-Nashta AA. Role of hyaluronic acid in maturation and further early embryo development of bovine oocytes. Theriogenology. 2012;78(3):670–7. doi: 10.1016/j.theriogenology.2012.03.013 22541325
47. Yokoo M, Shimizu T, Kimura N, Tunjung WAS, Matsumoto H, Abe H, et al. Role of the hyaluronan receptor CD44 during porcine oocyte maturation. J Reprod Dev. 2007;53(2):263–70. doi: 10.1262/jrd.18047 17135710
48. Opiela J, Romanek J, Lipinski D, Smorag Z. Effect of hyaluronan on developmental competence and quality of oocytes and obtained blastocysts from in vitro maturation of bovine oocytes. Biomed Res Int. 2014;2014):519189. doi: 10.1155/2014/519189 24689043
49. Keefer CL, Stice SL, Paprocki AM, Golueke P. In vitro culture of bovine IVM-IVF embryos: Cooperative interaction among embryos and the role of growth factors. Theriogenology. 1994;41(6):1323–31. doi: 10.1016/0093-691x(94)90491-z 16727487
50. Rios GL, Buschiazzo J, Mucci NC, Kaiser GG, Cesari A, Alberio RH. Combined epidermal growth factor and hyaluronic acid supplementation of in vitro maturation medium and its impact on bovine oocyte proteome and competence. Theriogenology. 2015;83(5):874–80. doi: 10.1016/j.theriogenology.2014.11.022 25497783
51. Furnus CC, Valcarcel A, Dulout FN, Errecalde AL. The hyaluronic acid receptor (CD44) is expressed in bovine oocytes and early stage embryos. Theriogenology. 2003;60(9):1633–44. doi: 10.1016/s0093-691x(03)00116-x 14580646
52. Bedaiwy MA, Mahfouz RZ, Goldberg JM, Sharma R, Falcone T, Abdel Hafez MF, Agarwal A. Relationship of reactive oxygen species levels in day 3 culture media to the outcome of in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril. 2010;94(6):2037–42. doi: 10.1016/j.fertnstert.2009.12.020 20138266
53. Kurzawa R, Glabowski W, Baczkowski T, Wiszniewska B, Marchlewicz M. Growth factors protect in vitro cultured embryos from the consequences of oxidative stress. Zygote. 2004;12(3):231–40. 15521713
54. Onodera Y, Teramura T, Takehara T, Fukuda K. Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes. FEBS Open Bio. 2015;5):476–84. doi: 10.1016/j.fob.2015.05.007 26106522
55. Kim Y, Lee Y-S, Choe J, Lee H, Kim Y-M, Jeoung D. CD44-epidermal growth factor receptor interaction mediates hyaluronic acid-promoted cell motility by activating protein kinase C signaling involving Akt, Rac1, Phox, reactive oxygen species, focal adhesion kinase, and MMP-2. J Biol Chem. 2008;283(33):22513–28. doi: 10.1074/jbc.M708319200 18577517
56. Rizos D, Ward F, Boland MP, Lonergan P. Effect of culture system on the yield and quality of bovine blastocysts as assessed by survival after vitrification. Theriogenology. 2001;56(1):1–16. doi: 10.1016/s0093-691x(01)00538-6 11467505
57. Rizos D, Gutierrez-Adan A, Perez-Garnelo S, La Fuente J de, Boland MP, Lonergan P. Bovine embryo culture in the presence or absence of serum: implications for blastocyst development, cryotolerance, and messenger RNA expression. Biol Reprod. 2003;68(1):236–43. doi: 10.1095/biolreprod.102.007799 12493719
58. Kuzmany A, Havlicek V, Wrenzycki C, Wilkening S, Brem G, Besenfelder U. Expression of mRNA, before and after freezing, in bovine blastocysts cultured under different conditions. Theriogenology. 2011;75(3):482–94. doi: 10.1016/j.theriogenology.2010.09.016 21144573
59. Gardner DK, Rodriegez-Martinez H, Lane M. Fetal development after transfer is increased by replacing protein with the glycosaminoglycan hyaluronan for mouse embryo culture and transfer. Hum Reprod. 1999;14(10):2575–80. doi: 10.1093/humrep/14.10.2575 10527990
60. Dattena M, Mara L, Bin T AA, Cappai P. Lambing rate using vitrified blastocysts is improved by culture with BSA and hyaluronan. Mol Reprod Dev. 2007;74(1):42–7. doi: 10.1002/mrd.20576 16929524
61. Thongkittidilok C, Tharasanit T, Songsasen N, Sananmuang T, Buarpung S, Techakumphu M. Epidermal growth factor improves developmental competence and embryonic quality of singly cultured domestic cat embryos. J Reprod Dev. 2015;61(4):269–76. doi: 10.1262/jrd.2014-167 25985792
62. Jackson RL, Busch SJ, Cardin AD. Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol Rev. 1991;71(2):481–539. doi: 10.1152/physrev.1991.71.2.481 2006221
63. Roy F, DeBlois C, Doillon CJ. Extracellular matrix analogs as carriers for growth factors: in vitro fibroblast behavior. J Biomed Mater Res. 1993;27(3):389–97. doi: 10.1002/jbm.820270312 8360207
64. Papakonstantinou E, Karakiulakis G, Roth M, Block LH. Platelet-derived growth factor stimulates the secretion of hyaluronic acid by proliferating human vascular smooth muscle cells. Proc Natl Acad Sci U S A. 1995;92(21):9881–5. doi: 10.1073/pnas.92.21.9881 7568237
65. Tirone E, D'Alessandris C, Hascall VC, Siracusa G, Salustri A. Hyaluronan synthesis by mouse cumulus cells is regulated by interactions between follicle-stimulating hormone (or epidermal growth factor) and a soluble oocyte factor (or transforming growth factor beta1). J Biol Chem. 1997;272(8):4787–94. doi: 10.1074/jbc.272.8.4787 9030534
66. Xu H, Wu K, Tian Y, Liu Q, Han N, Yuan X, et al. CD44 correlates with clinicopathological characteristics and is upregulated by EGFR in breast cancer. Int J Oncol. 2016;49(4):1343–50. doi: 10.3892/ijo.2016.3639 27499099
67. Zhang S, Chang MC, Zylka D, Turley S, Harrison R, Turley EA. The hyaluronan receptor RHAMM regulates extracellular-regulated kinase. J Biol Chem. 1998;273(18):11342–8. doi: 10.1074/jbc.273.18.11342 9556628
68. Stojkovic M, Krebs O, Kolle S, Prelle K, Assmann V, Zakhartchenko V, et al. Developmental regulation of hyaluronan-binding protein (RHAMM/IHABP) expression in early bovine embryos. Biol Reprod. 2003;68(1):60–6. doi: 10.1095/biolreprod.102.007716 12493696
69. Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005;6(1):56–68. doi: 10.1038/nrm1549 15688067
70. Yang Y, Du J, Hu Z, Liu J, Tian Y, Zhu Y, et al. Activation of Rac1-PI3K/Akt is required for epidermal growth factor-induced PAK1 activation and cell migration in MDA-MB-231 breast cancer cells. J Biomed Res. 2011;25(4):237–45. doi: 10.1016/S1674-8301(11)60032-8 23554696
71. Manser E, Huang HY, Loo TH, Chen XQ, Dong JM, Leung T, Lim L. Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol. 1997;17(3):1129–43. doi: 10.1128/mcb.17.3.1129 9032240
72. Chang F, Lemmon CA, Park D, Romer LH. FAK potentiates Rac1 activation and localization to matrix adhesion sites: a role for betaPIX. Mol Biol Cell. 2007;18(1):253–64. doi: 10.1091/mbc.E06-03-0207 17093062
73. Carisey A, Ballestrem C. Vinculin, an adapter protein in control of cell adhesion signalling. Eur J Cell Biol. 2011;90(2–3):157–63. doi: 10.1016/j.ejcb.2010.06.007 20655620
74. Memili E, First NL. Zygotic and embryonic gene expression in cow: a review of timing and mechanisms of early gene expression as compared with other species. Zygote. 2000;8(1):87–96. 10840878
75. Graf A, Krebs S, Heininen-Brown M, Zakhartchenko V, Blum H, Wolf E. Genome activation in bovine embryos: review of the literature and new insights from RNA sequencing experiments. Anim Reprod Sci. 2014;149(1–2):46–58. doi: 10.1016/j.anireprosci.2014.05.016 24975847
76. Sagirkaya H, Misirlioglu M, Kaya A, First NL, Parrish JJ, Memili E. Developmental and molecular correlates of bovine preimplantation embryos. Reproduction. 2006;131(5):895–904. doi: 10.1530/rep.1.01021 16672354
77. Wang Y, Jadhav RR, Liu J, Wilson D, Chen Y, Thompson IM, et al. Roles of Distal and Genic Methylation in the Development of Prostate Tumorigenesis Revealed by Genome-wide DNA Methylation Analysis. Sci Rep. 2016;6):22051. doi: 10.1038/srep22051 26924343
78. Doerfler W. On the biological significance of DNA methylation. Biochemistry (Mosc). 2005;70(5):505–24.
79. Long MD, Smiraglia DJ, Campbell MJ. The Genomic Impact of DNA CpG Methylation on Gene Expression; Relationships in Prostate Cancer. Biomolecules 2017. doi: 10.3390/biom7010015 28216563
80. Watt F, Molloy PL. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev. 1988;2(9):1136–43. doi: 10.1101/gad.2.9.1136 3192075
Článok vyšiel v časopise
PLOS One
2019 Číslo 10
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Úspěšná resuscitativní thorakotomie v přednemocniční neodkladné péči
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Correction: Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study
- Combining CDK4/6 inhibitors ribociclib and palbociclib with cytotoxic agents does not enhance cytotoxicity
- Experimentally validated simulation of coronary stents considering different dogboning ratios and asymmetric stent positioning
- Prevalence of pectus excavatum (PE), pectus carinatum (PC), tracheal hypoplasia, thoracic spine deformities and lateral heart displacement in thoracic radiographs of screw-tailed brachycephalic dogs